MLL rearrangements impact outcome in HOXA-deregulated T-lineage acute lymphoblastic leukemia: a Children’s Oncology Group Study

An early thymic precursor phenotype predicts outcome exclusively in HOXA-overexpressing adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study

“…In keeping with these findings, HOXA positivity has recently been reported to be associated with an ETP-like gene expression profile and induction failure in pediatric T-ALL. 34 Of note, the incidence of HOXA overexpression in that study was 25%, which is very similar to what we observed in this adult T-ALL cohort, and in excess of previous estimates of HOXA positivity based purely on transcriptomic clustering.…”

HOXA-activated early T-cell progenitor acute lymphoblastic leukemia: predictor of poor outcome?

“…Gene expression profiling to identify HOXA-activated T-ALL patients failed to classify 3 patients carrying HOXA-activating events in the COG series. 17 On the other hand, not all HOXA-activating genetic events have been resolved. 15 Also, what is the best method to identify ETP-ALL patients?…”

“…MLL-rearrangements combined with an ETP-ALL expression profile most strongly associated with induction failure, refractory disease and relapse. 17 Both studies therefore point to HOXA-activated ETP-ALL cases that are at a higher risk to fail on induction therapy or have inferior survival rates. Further studies are needed to investigate whether this can be attributed to specific HOXA-activating events: 13 HOXA-activated adult T-ALL patients that relapsed included 3 patients with SET-NUP214 fusions, 2 patients with MLLT10-rearrangements, 1 MLL-rearranged case and 1 patient with an inv(7), 15 while in the pediatric study the MLL-AF6 or Del3'MLL rearranged patients were at the highest risk to fail on therapy.…”

“…Further studies are needed to investigate whether this can be attributed to specific HOXA-activating events: 13 HOXA-activated adult T-ALL patients that relapsed included 3 patients with SET-NUP214 fusions, 2 patients with MLLT10-rearrangements, 1 MLL-rearranged case and 1 patient with an inv(7), 15 while in the pediatric study the MLL-AF6 or Del3'MLL rearranged patients were at the highest risk to fail on therapy. 17 Based on these important findings in both studies, routine screening for HOXA-activation events and ETP-ALL profiles in future T-ALL patients may help to identify patients at risk for induction failure or relapse. For this to happen, several issues need to be resolved: What would be the best detection method to identify HOXA-activated ETP-ALL patients?…”

“…In contrast, inv (7) 15 The Children's Oncology Group (COG) has now reported similar findings for pediatric T-ALL patients. 17 This study investigated 100 children with T-ALL who were treated in the COG AALL0434 protocol, including 17 patients for whom initial treatment failed. Evidence for MLL-rearrangements were found in 12 patients in addition to 6 CALM-AF10 + patients, 3 DDX3X-AF10 + patients (1 case had a complex CASK-DDX3X-AF10 translocation), 2 patients with NUP98-rearrangements and 3 inv(7)+ patients.…”